Introduction and background - PKU i MHPA

Phenylketonuria (PKU) is an inborn error of metabolism, characterized by mutations of the gene coding for phenylalanine hydroxylase (PAH)¹. PAH converts the amino acid phenylalanine (PHE) into tyrosine (TYR) and requires the cofactor tetrahydrobiopterin (BH4). The consequence of loss of PAH activity results in increased concentrations of phenylalanine in the blood and toxic concentrations in the brain, while TYR becomes semi-essential.

In the dietary management of PKU, the main principle is to reduce the blood PHE concentrations by early institution of restricted dietary PHE intake. This dietary management of PKU has shown to be essential to optimize outcome and avoid the potential consequences of poor metabolic control e.g. progressive intellectual impairment, accompanied by additional symptoms, including autism, seizures and motor deficits.¹ Mainstay management consists of dietary restriction of PHE, by restriction of protein containing foods and additionally a PHE-free protein substitutes must be provided to compensate for the resulting deficiencies in the other essential and non-essential amino acids and micronutrients².

PKU was the first inborn error of metabolism that identified affected individuals by Newborn Screening. Early diagnosis of PKU through new born screening in the first days of life is now established in most Western countries in the world. If immediate initiation of appropriate dietary intervention consequently is initiated, it will prevent children with PKU from neuropathological effects and a lifetime of mental retardation.

Children with the most severe form, classical PKU, not managed by a PHE restricted diet, develop severe intellectual disability, seizures, ataxia, motor deficits and behavioral problems. From an age of about 6 months these children exhibit developmental problems possibly accompanied by behavioral issues, including self-harm, aggression and psychosis¹.

Young children with a late diagnosis of PKU display marked and rapid benefit of dietary intervention. However, most retain some degree of intellectual disability and almost all display significant disabilities, disrespect of the improvement in IQ.³

The incidence of PKU varies between countries in the world. In general in Europe the incidence is 1:10.000 and the US 1:13.000. A much higher incidence is seen in eg Turkey 1:4.200, But also much lower is seen in Thailand 1:200.000.

Nutrica supports ‘diet for life’ for all patients with PKU. Research has shown that adherence to a well-managed diet plan has the best possible clinical outcomes for patients with PKU. However, diet compliance continues to be a major issue among patients with PKU, often starting in pre-adolescence.

References

Blau N, van Spronsen FJ, Levy HL. Lancet 2010;376:1417-1427
Van Spronsen FJ, Huijbregts SC, Bosch AM et al. Cognitive, neurophysiological, neurologica and psychosocial outcomes in early-treated PKU patients: a start towards standardized outcome measurements accross development. Mol Genet Metab 2011;104(suppl):S45-51
Gentile JK et al. Psychological aspects of PKU: hidden disabilities, a review. Mol Genet Metab. 2010;99(S1):64-67